US2842571A - Method of obtaining steroid hormone derivatives substituted in the 4-position - Google Patents

Method of obtaining steroid hormone derivatives substituted in the 4-position Download PDF

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Publication number
US2842571A
US2842571A US618438A US61843856A US2842571A US 2842571 A US2842571 A US 2842571A US 618438 A US618438 A US 618438A US 61843856 A US61843856 A US 61843856A US 2842571 A US2842571 A US 2842571A
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steroid
steroid hormone
keto
epoxy
derivatives substituted
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US618438A
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Camerino Bruno
Patelli Bianca
Vercellone Alberto
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Pfizer Italia SRL
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Farmaceutici Italia SpA
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J13/00—Normal steroids containing carbon, hydrogen, halogen or oxygen having a carbon-to-carbon double bond from or to position 17
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J75/00—Processes for the preparation of steroids in general

Definitions

  • Example 1 A -pregnene-4-0Z-3,2O-dione l g. 4,9,5-epoxy-pregnane-3,20-dione, M. P. 135 C., is dissolved in 25 cc. of anhydrous benzene, 0.435 g. of boron trifluoride-etherate are added and the reaction mixture is left standing overnight. It is then treated with a sodium bicarbonate solution, washed with water and dried. The residue, obtained upon distilling of the henzene, is recrystallized from methylalcohol and yields 350 mg. A -pregnene-4-ol-3,2O-dione, M. P. 225-230 C. The product does not lower the melting point when mixed with a standard sample obtained according to said copending application.
  • Example 2. -A -pregnene-4-0l-3,20-di0ne 1 g. 234-235 C., are treated as in Example 1. 150 mg. A -pregnene-4-ol-3,ZO-dione, M. P. 228-232 C., are obtained, which are identical with the product of Example 1.
  • Example 3 A -pregnene-4,21-diol-3,20-dione Proceeding as in Example 1, from 1 g. 4,8,5-epoxy-pregnane-21-ol-3,20-di*0ne, M. P. 142-143 C., 400 mg. A pregnene-4,21-di0l-3,20-di0ne, M. P. 210212 C., are obtained.
  • R" represents a member of the group consisting of OH and acyloxy, which comprises dissolving a 4,5-epoxy3-keto-steroid of the general formula in an organic solvent, treating with boron tn'fluoride and recovering the 4-substituted steroid hormone.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Steroid Compounds (AREA)

Description

United States Patent Ofilice 2,842,571 Patented July 8, 1955 METHOD OF OBTAINING STERDID HORMONE DIESRIVATIVES SUBSTITUTED IN THE 4-POSI- T N Bruno Camerino, Bianca Patelli, and Alberto Vercellone, Milan, Italy, assignors to Societa Farmaceutici Italia, a corporation of Italy No Drawing. Application October 26, 1956 Serial No. 618,438
Claims priority, application Italy March 29, 1956 6 Claims. (Cl. 260-39145) 0d of Preparing Same, of which this application is a 5 continuation-impart, a method has been described and claimed for preparing compounds of the general formula are obtained by reacting a 4,5-epoxy-3-keto-steroid (a and B epimers) of the general formula with mineral acids in :an organic solvent.
By reacting, for example, a 4,9,5-epoxy-3-keto-Lsteroid or a 4a,5-epoxy-3-keto-steroid with either conc. sulfuric acid in anhydrous acetic acid, or with aqueous hydrofluoric acid in acetic acid or with diluted sulfuric acid in methyl alcohol or benzene, :a 4-hydroxy-3-keto-A -steroid (enol-forrn) or the equivalent 3,4-diketo-steroid (ketoform) is obtained according to the following reaction scheme We have found now that the same results can be obtained, with the same starting materials and at equal yields, by using boron trifiuoride, in the form of either an etherate or a similar complex, in an organic solvent, instead of mineral acid, such as conc. H 50 This procedure has the advantage of avoiding a strong acidic mediurn which, in some cases, could damage or further convert the starting material. For example, according to Examples 9, 10, 11, 12, 13 of said co-pending application, by treating 4,5-epoxides of testosterone and desoxycorticosterone with H 80 and acetic acid, the 17- lacetates and the ZI-acetates of the 4-hydroxy-steroid are obtained, whereas when proceeding according to the process of the present application, 4-hydroxy-steroids are obtained which have a free alcoholic group in the 17- and 21-positions.
The following examples are presented to illustrate the present invention without limiting its scope Example 1.-A -pregnene-4-0Z-3,2O-dione l g. 4,9,5-epoxy-pregnane-3,20-dione, M. P. 135 C., is dissolved in 25 cc. of anhydrous benzene, 0.435 g. of boron trifluoride-etherate are added and the reaction mixture is left standing overnight. It is then treated with a sodium bicarbonate solution, washed with water and dried. The residue, obtained upon distilling of the henzene, is recrystallized from methylalcohol and yields 350 mg. A -pregnene-4-ol-3,2O-dione, M. P. 225-230 C. The product does not lower the melting point when mixed with a standard sample obtained according to said copending application.
Example 2.-A -pregnene-4-0l-3,20-di0ne 1 g. 234-235 C., are treated as in Example 1. 150 mg. A -pregnene-4-ol-3,ZO-dione, M. P. 228-232 C., are obtained, which are identical with the product of Example 1.
Example 3.-A -pregnene-4,21-diol-3,20-dione Proceeding as in Example 1, from 1 g. 4,8,5-epoxy-pregnane-21-ol-3,20-di*0ne, M. P. 142-143 C., 400 mg. A pregnene-4,21-di0l-3,20-di0ne, M. P. 210212 C., are obtained.
For C H O Found: 72.82% C; 8.88% H. Calc.: 72.80% C; 8.73% H.
Upon acetylating, in the usual manner, A -pregnene- 4,2l-diol-3,20-dione diacetate, M. P. 198200 C., is obtained, identical with a standard sample obtained according to said co-pending application.
Example 4.A -andr0stene-4,1 7B-diol-3-0ne 4u,5-epoxy-allopregnane-3,11,20-trione, M. P.
wherein R represents a member of the group consisting of =0, (H)OH, (H)COCH (H)COCH OH and (OH)COCH OH, R represents a member of the group consisting of H (H) OH and =0, and R" represents a member of the group consisting of OH and acyloxy, which comprises dissolving a 4,5-epoxy3-keto-steroid of the general formula in an organic solvent, treating with boron tn'fluoride and recovering the 4-substituted steroid hormone.
2. The process according to claim 1, wherein said 4,5- epoxy-3-keto-steroid is dissolved in benzene and boron trifluoride is added in form of an etherate.
3. The process according to claim 2, wherein a member of the group consisting of 4-hydr0xy-3-ket0-A steroid (enol-form) and 3,4-diketo-steroid (keto-form) is obtained upon using 4,5-epoxy-3-keto-steroid as starting material.
4. The process according to claim 3, wherein said 4,5- epoxy-3-keto-steroid is a 4;8,5,B-epoxide.
5. The. process according to claim 3, wherein said 4,5-epoxy-3-keto-steroid is a 4a,5e-epoxide.
'6. The process according to claim 3 wherein said 4,5-epoxy-3-keto-steroid is a mixture of 43,5,3- and 4oz, 5a-epoxides.
' No references cited.

Claims (1)

1. THE PROCESS OF PREPARING A 4-SUBSTITUTED STEROID HORMONE DERIVATIVE OF THE GENERAL FORMULA
US618438A 1956-03-29 1956-10-26 Method of obtaining steroid hormone derivatives substituted in the 4-position Expired - Lifetime US2842571A (en)

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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3020295A (en) * 1959-07-13 1962-02-06 Farmaceutici Italia Therapeutic 4-hydroxy-19-nortestosterone-17-cyclopentyl-propionate and its process of preparation and its application
US3025310A (en) * 1956-05-21 1962-03-13 Farmaceutici Italia Process for preparing 19-nortestosterone derivatives substituted in the 4-position and products of high anabolic activity obtained thereby
US3146239A (en) * 1957-09-23 1964-08-25 Syntex Corp 4-halo-19-nor-progesterone
US3324171A (en) * 1964-04-13 1967-06-06 Squibb & Sons Inc A-norsteroids

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
None *

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3025310A (en) * 1956-05-21 1962-03-13 Farmaceutici Italia Process for preparing 19-nortestosterone derivatives substituted in the 4-position and products of high anabolic activity obtained thereby
US3146239A (en) * 1957-09-23 1964-08-25 Syntex Corp 4-halo-19-nor-progesterone
US3020295A (en) * 1959-07-13 1962-02-06 Farmaceutici Italia Therapeutic 4-hydroxy-19-nortestosterone-17-cyclopentyl-propionate and its process of preparation and its application
US3324171A (en) * 1964-04-13 1967-06-06 Squibb & Sons Inc A-norsteroids

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